ClinVar Miner

Submissions for variant NM_021971.4(GMPPB):c.95C>T (p.Pro32Leu)

gnomAD frequency: 0.00001  dbSNP: rs397509426
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
HudsonAlpha Institute for Biotechnology, HudsonAlpha Institute for Biotechnology RCV000209926 SCV000265551 pathogenic Autosomal recessive limb-girdle muscular dystrophy type 2T 2015-01-13 criteria provided, single submitter research
GeneDx RCV000493576 SCV000581791 pathogenic not provided 2024-01-12 criteria provided, single submitter clinical testing Published functional studies demonstrate dysfunctional GMPPB protein as the P32L variant caused the protein to form aggregates in the cytoplasm (PMID: 23768512); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Missense variants in this gene are a common cause of disease and they are underrepresented in the general population; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 23768512, 26310427, 24780531, 33060286, 34749429, 19901254, 25681410, 28554332, 28456886, 29437916, 30257713, 37681231, 35006422)
Labcorp Genetics (formerly Invitae), Labcorp RCV000684892 SCV000812353 pathogenic Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A14; Muscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type B14; Autosomal recessive limb-girdle muscular dystrophy type 2T 2025-01-19 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 32 of the GMPPB protein (p.Pro32Leu). This variant is present in population databases (rs397509426, gnomAD 0.02%). This missense change has been observed in individual(s) with GMPPB-related conditions (PMID: 23768512, 25681410, 28554332, 30257713). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 60544). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is expected to disrupt GMPPB protein function with a positive predictive value of 80%. Experimental studies have shown that this missense change affects GMPPB function (PMID: 23768512). For these reasons, this variant has been classified as Pathogenic.
Revvity Omics, Revvity RCV000493576 SCV002018483 pathogenic not provided 2022-08-03 criteria provided, single submitter clinical testing
OMIM RCV000054438 SCV000082915 pathogenic Muscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type B14 2013-07-11 no assertion criteria provided literature only

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